Multivariate patterning of human pluripotent cells reveals induced paracrine factors in kidney organoid development

phys.org | 8/20/2019 | Staff
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Bioengineers have shown great promise in creating complex multicellular kidney organoids (tiny, self-organized tissues) in the lab using pluripotent stem cells . They can further improve the procedure for different outcomes, including patterning and maturation of specific cell types, although such experiments are limited by standard tissue culture approaches. Now writing in Science Advances, Nick R. Glass and an interdisciplinary research team at the Australian Institute for Bioengineering and Nanotechnology, Murdoch Children's Research Institute and the Department of Pediatrics and Biomedical Manufacturing in Australia detailed a new full factorial microbioreactor array-based method to perform complex differentiation in the lab.

Using the method, they rapidly interrogated and optimized the complex cell differentiation and development process in a simplistic setup. Glass et al. successfully recapitulated early kidney tissue patterning events and explored more than 1000 unique conditions to achieve near-pure renal cell type specification. The team conducted single-cell resolution identification of distinct renal cell types within multilayered kidney organoids and coupled the results with multivariate analysis to define the roles of several signaling proteins. The bioengineers also noted retinoic acid (RA) as a minimal effect of nephron patterning, while highlighting contributions of induced paracrine factors on cell specification and patterning.

Kidney - Development - Stem - Cell - Types

The mammalian kidney is formed during early embryonic development from two different stem cell types; one to generate collecting ducts and the other to form functional filtering units of the kidney known as nephrons. More specifically, the mammalian kidney is a byproduct of the intermediate mesoderm (IM), arising through inductive interactions between several key progenitor (stem cell-like) IM subpopulations. While the anterior IM-derived epithelial nephric duct formed the ureter and collecting ducts of the kidney. The filtering units of the kidney or nephrons typically arose via epithelial transformations of the posterior IM known as the metanephric mesenchyme (MM). Scientists have studied normal mammalian kidney...
(Excerpt) Read more at: phys.org
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